The principal objective of this research proposal is the determination of the three dimensional structure of protein molecules using x-ray diffraction analysis of their crystals, in particular the structure analysis of turkey egg white lysozyme, bobwhite quail lysozyme and an intact human immunoglobulin are being undertaken. Turkey lysozyme differs from hen lysozyme among other positions in an ASP to GLY subsitution at the active cleft of the enzyme thereby altering the mode of binding of the substrate. Structure analysis of the NAG-NAG-NAG turkey lysozyme complex crystals will reveal the nature of this altered binding and its effect on the activity of the enzyme. Immunochemical studies on bobwhite lysozyme indicate a conformational change occuring as a result of three minor amino acid substitutions in the interior of the protein. Its structure analysis will prove this quite conclusively in addition to judging the sensitivity of immunochemical tests used to determine structural resemblance between homologous proteins. Rotation function methods will be used in the structure analysis of lysozymes. Structure of immunoglobulin crystals will be carried out on two human myeloma proteins (DOB and RETI). The diffraction pattern of DOB immunoglobulin crystals have been extended to 4A resolution by cocrystallizing the protein with certain bifunctional reagents. RETI crystals give a diffraction pattern to a resolution of 3.5A. The structure analysis will reveal the structures of the Fab and the Fc fragments, their spatial arrangement in the complete structure, the structure of the antigen binding site, the nature of a possible antigen - antibody interaction and perhaps a mechanism for the basic recognition of one molecule by another. Crystals have already been grown for the turkey lysozyme inhibitor complex and the two immunoglobulins.